The gradual development of facial wrinkles, whether fine surface lines or deeper creases and folds, is the classic early sign of accumulated skin damage and aging. Premature aging and wrinkling of the skin may be accelerated by excessive exposure to the sun and other elements, overactive facial expression muscles, the frequent use of tobacco products, poor nutrition, or skin disorders. Fine surface wrinkles that progress to deeper creases, deepening facial expression due to repeated skin folding, and deep folds which develop with one's maturity are obvious changes which may combine to portray a less desirable appearance. Several invasive techniques are available in which substances are injected or implanted in the area of the skin which either temporarily weaken the muscles or act as skin volume fillers, however non-invasive treatments have historically met with only minimal success. Regardless of the cause of facial creases or folds, safe and effective treatments for reduction or elimination of these problems has been exceedingly difficult to achieve.
Skin elasticity is critical for improving damage such as sagging, reduced skin firmness and youthful appearance, and improving the appearance of fine lines and wrinkles. All these are made possible by elastin, a protein polymer that works like a rubber band, repeatedly stretching and contracting without suffering any damage.
Elastin polymers are formed by the cross-linking of tropoelastin monomers. Although there are as many as five enzymes that can catalyze this process, it is unclear exactly how the crosslinking is regulated. Li and colleagues have reported that one of these enzymes, lysyl oxidase-like 1 (LOXL1) is essential for remodeling elastin fibers. Liu and colleagues predicted that the enzyme is recruited to sites of elastin by the extracellular-matrix protein fibulin-5. LOXL1 then primes tropoelastin monomers (TE) for incorporation into the larger polymer. Liu found that LOXL1 is necessary to prevent age-related loss of elasticity in tissues such as arteries and lungs (Liu, et al. (2004) Elastic fiber homeostasis requires lysyl oxidase-like 1 protein. Nat Genet. 36(2):178-82).
Noblesse, et al. have shown that LOXL1 is present in the dermis and the epidermis of both normal skin and in a skin equivalent model (SE). The ultrastructural localization of LOXL was indicative of its association with elastin-positive materials. The investigators hypothesized that LOXL could have a role in elastic fiber formation (Noblesse E, et al. (2004) Lysyl oxidase-like and lysyl oxidase are present in the dermis and epidermis of a skin equivalent and in human skin and are associated to elastic fibers. J Invest Dermatol. 122(3):621-30).
Pascual and colleagues have shown levels of markers of elastin synthesis including LOXL1 diminish to a significant extent with age (Pascual, et al. (2008) Down-regulation of lysyl oxydase-like in aging and venous insufficiency. Histol Histopathol. 23(2): 179-86).
U.S. Patent Pub. No. 2005/0188427 by Li and Liu discloses a method of treating a subject having a condition associated with a loss of elastic fibers, such as loose or wrinkly skin, comprising administering to the subject a therapeutically effective amount of a LOXL1 enhancer. The LOXL1 enhancers are said to be LOXL1 polypeptides or active fragments thereof, or a nucleic acid encoding a LOXL1 polypeptide or active fragment thereof. The LOXL1 enhancers are also said to include small molecules or other therapeutic compounds identified by the screening method disclosed in that publication.
Desthiobiotin has been known since the mid-1940's as a precursor of biotin in bacteria and molds (see Leonian and Lilly (1945) Conversion of Desthiobiotin Into Biotin or Biotinlike Substances by Some Microorganisms. J Bacteriol. 49(3): 291-297). Desthiobiotin is derived from biotin by the removal of the sulfur atom. It can substitute for biotin in some microorganisms, but is without effect on or is inhibitory to the growth of others. The compound has the following structure:

U.S. Pat. No. 4,243,665 describes the use of low concentrations of certain biotin derivatives in tooth care. This patent is based on the idea that compounds such as desthiobiotin can biotin-deplete microorganisms that cause dental decay.
U.S. Pat. No. 4,529,587 to Lever Brothers Corp. describes the use of certain biotin antagonists for decreasing sebum synthesis. These compounds have the general structure:
and are described as blocking biotin dependent enzymes that are implicated in lipid synthesis, in particular in their effect against acetyl-SCoA-carboxylase. The compositions are said to be useful for reducing superficial “grease” without defatting the skin.
There remains a need for cosmetic compositions which reduce signs of aging including sagging, reduced elasticity, fine lines and wrinkles, particularly on the skin of the face, neck, hands, etc.
It is therefore an object of the present invention to provide improved compositions and methods of use to improve the appearance of skin, including by reducing the appearance of fine lines and wrinkles.